Medications are an integral part of modern medicine. They save lives, relieve symptoms, and improve the quality of life for many patients. However, their impact on the hormonal balance is often underestimated. Testosterone levels, in particular, can be significantly affected by various active ingredients.
A low testosterone level does not always manifest itself immediately and clearly. Typical symptoms include loss of libido, reduced performance, lack of motivation, depressive mood, muscle loss, or an increase in body fat (Wu et al., 2010). Since these symptoms are nonspecific, the cause is often not suspected to be hormonal. The connection with existing medication therefore often remains undetected.
The following article highlights which classes of medications can affect testosterone levels, the mechanisms behind them, and why early hormonal monitoring is advisable.
How is testosterone regulated in the body? The HPG axis explained simply
To understand how medications can affect testosterone levels, it is helpful to know the natural hormonal control.
Testosterone production does not begin in the testes themselves, but in the brain. More precisely, in a small region called the hypothalamus. This structure acts as the body's central hormonal control center.
Step 1: The start in the brain
The hypothalamus releases a hormone called GnRH. This hormone is essentially the starting signal for testosterone production.
Step 2: Transmission to the pituitary gland
GnRH reaches the pituitary gland. There, it causes the release of another hormone: LH, luteinizing hormone.
Step 3: Production in the testes
LH acts directly on the so-called Leydig cells in the testes. These specialized cells then produce testosterone.
This three-step regulation is known as the hypothalamus-pituitary-gonadal axis, or HPG axis for short (Bhasin et al., 2018).
The principle of (negative) feedback
In addition, there is a feedback mechanism:
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If testosterone levels in the blood rise, the brain detects this and reduces GnRH and LH release.
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If testosterone levels fall, production is stimulated again.
This finely tuned system normally ensures stable hormone levels (“Textbook of Endocrine Physiology,” 2011).
However, if any of these levels are disrupted by medications, stress, chronic illnesses, or other influences, the entire axis can become unbalanced. This is precisely where many of the active ingredients described later come into play.
Which medications can affect testosterone levels?
In addition to so-called androgen deprivation therapy, which, for example in prostate cancer, has the explicit medical aim of lowering testosterone levels with medication, a variety of other active ingredients can also negatively affect testosterone levels as an unwanted side effect. In addition to strong painkillers, known as opioids, antihypertensives (e.g., beta-blockers), antidepressants (especially the group of selective serotonin reuptake inhibitors, known as SSRIs), and antipsychotics can also affect testosterone levels. The extent of the impact varies from person to person, and the corresponding mechanisms of the active ingredients differ. Furthermore, the duration of use, age, weight, and co-existing conditions can play a role (Basaria, 2014).
This list already shows how broad the range of potentially relevant medications is. This is particularly relevant for men with chronic illnesses, as several active ingredients are often used simultaneously.
Opioids and the suppression of the HPG axis
Chronic pain patients who receive opioids for extended periods are at a particularly high risk of hormonal suppression. This includes active ingredients such as morphine, oxycodone, hydromorphone, fentanyl, tilidine, and tramadol. These medications are often used for chronic back pain, cancer pain, or neuropathic pain. The effect can occur after just a few weeks or months and is by no means rare in practice (Coluzzi et al., 2018).
Opioids lower testosterone levels by activating specific receptors in the hypothalamus, a special region in the brain that acts as a higher-level hormonal control center, thereby suppressing the hypothalamus-pituitary-gonadal axis or consequently reducing the hormonal stimulation of the testes (Kafel et al., 2025).
Simply put, opioids not only relieve pain but also affect the hormonal control center in the brain. The signaling chain from the hypothalamus through the pituitary gland to the testes is slowed down. As a result, the testes receive less stimulus for testosterone production (Daniell, 2002).
This so-called opioid-induced androgen deficiency is well documented and can significantly impair libido, energy, muscle mass, and mood (Abs et al., 2000).
Typical symptoms include fatigue, loss of libido, reduced strength, or depressive mood (Basaria et al., 2015). Since these symptoms also frequently occur in chronic pain patients, the hormonal component is not always recognized in practice. Targeted laboratory monitoring can provide clarity here.
Antidepressants and serotonergic mechanisms
Antidepressants can also have hormonal effects.
Antidepressants such as the group of so-called SSRIs increase serotonergic activity and thus inhibit the GnRH-producing neurons or consequently the hormonal release in the pituitary gland. Furthermore, by inhibiting dopamine-producing neurons, they can indirectly increase prolactin levels (Corona et al., 2009).
This complex neuroendocrine interaction shows that the impact is not only direct on the testes but is also mediated through central regulatory mechanisms in the brain. Therefore, in the case of long-term use, a hormonal component should also be considered if corresponding symptoms occur.
Antipsychotics and the impact via prolactin
Antipsychotics such as risperidone or haloperidol can increase prolactin levels and thus consequently lower testosterone levels (Molitch, 2005).
Prolactin inhibits the release of GnRH in the hypothalamus. As a result, LH and FSH from the pituitary gland decrease, thereby reducing the stimulation of the testosterone-producing Leydig cells in the testes. Testosterone production decreases. Clinically, this can manifest as loss of libido, erectile dysfunction, or fertility disorders (Holt & Peveler, 2010).
Glucocorticoids and direct effects on the testes
Corticosteroids are used in many conditions, for example in asthma, rheumatism, or autoimmune diseases.
Glucocorticoids (e.g., prednisolone or dexamethasone) can also suppress the body's own testosterone production by inhibiting the hypothalamus-pituitary-gonadal axis, as well as have a direct negative effect on the testosterone-producing cells in the testes. These effects are particularly relevant with prolonged use or systemic therapy (Whirledge & Cidlowski, 2013).
Two mechanisms act simultaneously here: the central control is dampened, and the Leydig cells in the testes can also be directly affected.
Why is medication-induced testosterone deficiency often overlooked?
Medication-induced testosterone deficiency, or the impact of various active ingredients on the hormonal control of testosterone production, is well documented and pathophysiologically understood. However, the symptoms are often overlooked in clinical practice, or information about them is often inadequate, because the treatment of the underlying condition takes precedence. It is therefore important to discuss the topic with patients and to perform an early test of testosterone levels.
If you want to know how a testosterone test works and which values are important, read our article “Step-by-Step Guide to the Testosterone Test”.
In practice, the focus understandably lies on the underlying condition. Fatigue or loss of libido are then often attributed to depression, pain syndrome, or age. Targeted laboratory monitoring often occurs only late.
When should hormonal assessment be carried out?
Hormonal diagnostics are advisable in cases of:
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newly occurring loss of libido
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unexplained fatigue
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reduced performance
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depressive symptoms
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long-term therapy with opioid painkillers
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therapy with antipsychotics or SSRIs
Relevant laboratory parameters include:
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free testosterone
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if applicable, prolactin
Interpretation in the clinical context is important. An isolated laboratory value without consideration of symptoms and co-existing conditions is not sufficient (MALE HYPOGONADISM - UROWeB, n.d.).
You can find more on the topic of testosterone deficiency in our article “Testosterone Deficiency in Men: Causes, Symptoms, and Solutions”.
Therapeutic considerations
A change in medication is not always possible or advisable. In some cases, a dose adjustment, a change of active ingredient, or complementary hormonal therapy may be considered. This decision should always be made individually and interdisciplinarily.
Especially with the long-term use of hormone-relevant medications, regular monitoring of endocrine parameters is recommended to detect a gradual development early.
Our conclusion, your knowledge
Medications can have a significant impact on the male hormonal balance. In addition to oncological therapies, opioids, antidepressants, antipsychotics, antihypertensives, and glucocorticoids are particularly relevant.
Medication-induced testosterone deficiency is well explained pathophysiologically, but is often not sufficiently considered in everyday clinical practice. Men with corresponding symptoms should therefore not hesitate to have their medication critically reviewed and, if necessary, have a hormonal assessment carried out.
Open communication with the doctor and targeted laboratory diagnostics are crucial to avoid long-term health consequences and maintain quality of life.
